HIPK2 protects neurons from oxidative stress and modulates central nervous system responses following traumatic brain injury
نویسندگان
1 Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical, Quanzhou , Fujian Province, China
2 Department of Intensive Care Unit, The Second Affiliated Hospital of Fujian Medical, Quanzhou, Fujian Province, China
3 Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical, Quanzhou, Fujian Province, China
4 Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical, Quanzhou, Fujian Province, China
5 Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical, Quanzhou, Fujian Province, China
6 Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical, Quanzhou, Fujian Province, China
doi
10.22038/ijbms.2026.90522.19511چکیده
Objective(s): Traumatic brain injury (TBI) induces oxidative stress, contributing to secondary neuronal damage. This study aimed to elucidate the role of the stress-responsive kinase HIPK2 in regulating endogenous antioxidant defenses in neural tissue following TBI.Materials and Methods: We employed complementary in vitro and in vivo models: an H₂O₂-induced oxidative stress model in PC12 cells (with HIPK2 inhibited by tBID) and a controlled cortical impact mouse model of TBI (with HIPK2 overexpressed via intracerebroventricular Ad-HIPK2 injection). Analyses included assessments of cell viability, mRNA expression, and protein levels of key antioxidant factors (HO-1, UGT1A1, NQO1).Results: In vitro, HIPK2 inhibition markedly increased oxidative stress-induced cell death and significantly down-regulated UGT1A1 expression. In vivo, endogenous HIPK2 expression was significantly suppressed post-TBI. Conversely, HIPK2 overexpression effectively rescued the expression of antioxidant proteins UGT1A1 and NQO1. Conclusion: These results demonstrate that HIPK2 is a critical modulator of the antioxidant response after TBI, capable of orchestrating key defense genes and conferring neuroprotection. Our findings identify HIPK2 as a promising molecular target for therapeutic intervention against TBI-related oxidative damage.
